Establishment and Application of Hepatitis B Virus Persistent Replication Model in IFNAR-/- Mouse

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 33; no. 3; pp. 392 - 397
• Main Author: 陈明发 林永 夏幼辰 孙潺 冯雪梅 陆蒙吉 杨东亮 吴珺
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01.06.2013; Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan 430022, China; Department of Infectious Diseases, the Second Affiliated Hospital, Nanchang University, Nanchang 330006, China%Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan 430022, China%Institute of Virology, Medical School of Duisburg-Essen University, Essen 45122, Germany
• Subjects: Animals; Chronic Disease; Disease Models, Animal; DNA水平; Female; Hepatitis B - genetics; Hepatitis B - virology; Hepatitis B virus - physiology; Humans; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptor, Interferon alpha-beta - genetics; Receptor, Interferon alpha-beta - metabolism; Virus Replication - genetics; 乙肝病毒; 功能类型; 复制; 小鼠模型; 应用; 抗HBV; 病毒感染; chronic hepatitis B; mouse; type I interferon receptor (IFNAR); animal model; IFNAR; type I Interferon; type Ⅰ Interferon; type Ⅰ interferon receptor (IFNAR); IFNAR-/-mouse
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-013-1130-y

Summary： The type I interferon and IFNAR play an important role in hepatitis B virus （HBV） infection and anti-HBV therapy. However, its mechanism of action is still poorly understood. To gain more in- sights into the role of type I interferon and type I interferon receptor （IFNAR） in HBV infection, we established an HBV persistent replication IFNAR knockout （IFNAR-/-） mouse model and preliminarily applied this model. At first, the progeny of IFNAR-/- mouse was reproduced. Then hydrodynamic injec- tion with pAAV/HBV1.2 plasmid was conducted to establish the persistent HBV replication IFNAR-/- mouse model. At last, we applied this model to evaluate the effect of nucleoside analogues entecavir （ETV） on HBV replication. It was found that there was no difference in the serum HBsAg and HBeAg levels and HBcAg expression in the liver tissue between the ETV treated groups and normal saline （NS） treated group, but the serum HBV DNA levels were significantly suppressed 10, 25, 40 and 55 days af- ter the ETV treatment [P=0.035, P=0.00, P=0.149 and P=-0.084, IFNAR knockout （KO） control group vs. C57BL/6 ETV groups, respectively; P=0.081, P=0.001, P=0.243 and P=-0.147, IFNAR KO control group vs. IFNAR KO ETV groups, respectively]. Interestingly, there was no difference in serum HBV DNA levels between the ETV treated IFNAR/- and C57BL/6 mice. This result suggests that HBV sup- pression during ETV treatments doesn＇t depend on type Ⅰinterferon and IFNAR. Collectively, persis- tent HBV replication IFNAR/ mouse model that we established is a useful and convenient tool to detect the function of the type Ⅰ interferon and IFNAR in HBV infection and anti-HBV treatments.